At-Risk Variant in TCF7L2 for Type II Diabetes Increases Risk of Schizophrenia

被引：108

作者：

Hansen, Thomas ^{[1
,2
]}

Ingason, Andres ^{[1
]}

Djurovic, Srdjan ^{[3
]}

Melle, Ingrid ^{[3
,4
]}

Fenger, Mogens ^{[5
]}

Gustafsson, Omar ^{[6
]}

Jakobsen, Klaus D. ^{[1
,2
,7
]}

Rasmussen, Henrik B. ^{[1
]}

Tosato, Sarah ^{[8
]}

Rietschel, Marcella ^{[9
]}

Frank, Josef ^{[9
]}

Owen, Mike ^{[10
]}

Bonetto, Chiara ^{[8
]}

Suvisaari, Jaana ^{[11
,12
,13
]}

Thygesen, Johan Hilge ^{[1
]}

Petursson, Hannes ^{[14
]}

Lonnqvist, Jouko ^{[11
,12
,13
]}

Sigurdsson, Engilbert ^{[14
]}

Giegling, Ina ^{[15
]}

Craddock, Nick ^{[10
]}

O'Donovan, Michael C. ^{[10
]}

Ruggeri, Mirella ^{[8
]}

Cichon, Sven ^{[16
,17
]}

Ophoff, Roel A. ^{[18
,19
,20
]}

Pietilainen, Olli ^{[11
,12
,13
]}

Peltonen, Leena ^{[11
,12
,13
,21
,22
,23
]}

Noethen, Markus M. ^{[24
]}

Rujescu, Dan ^{[15
]}

St Clair, David ^{[25
]}

Collier, David A. ^{[26
]}

Andreassen, Ole A. ^{[4
,6
]}

Werge, Thomas ^{[1
]}

机构：

[1] Copenhagen Univ Hosp, Res Inst Biol Psychiat, Mental Hlth Ctr Sct Hans, Boserupvej 4, DK-4000 Roskilde, Denmark

[2] Univ Copenhagen, Ctr Pharmacogenom, Copenhagen, Denmark

[3] Univ Oslo, Oslo Univ Hosp Ulleval, Dept Med Genet, Oslo, Norway

[4] Univ Oslo, Inst Psychiat, TOP Project, Oslo, Norway

[5] Copenhagen Univ Hosp, Dept Clin Biochem, Hvidovre, Denmark

[6] Oslo Univ Hosp Ulleval, Dept Psychiat, Oslo, Norway

[7] Copenhagen Univ Hosp, Psychiat Ctr Hvidovre, Hvidovre, Denmark

[8] Univ Verona, Sect Psychiat & Clin Psychol, Dept Publ Hlth & Community Med, I-37100 Verona, Italy

[9] Univ Mannheim, Cent Inst Mental Hlth, Dept Genet Epidemiol Psychiat, Mannheim, Germany

[10] Cardiff Univ, Sch Med, Dept Psychol Med, Cardiff, S Glam, Wales

[11] Univ Helsinki, Inst Mol Med Finland FIMM, Helsinki, Finland

[12] Univ Helsinki, Natl Inst Hlth & Welf, Helsinki, Finland

[13] Univ Helsinki, Dept Med Genet, Helsinki, Finland

[14] Natl Univ Hosp Reykjavik, Dept Psychiat, Reykjavik, Iceland

[15] Univ Munich, Div Mol & Clin Neurol, Munich, Germany

[16] Forschungszentrum Julich, Inst Neurosci & Med, D-52425 Julich, Germany

[17] Univ Bonn, Life & Brain Ctr, Dept Genom, D-5300 Bonn, Germany

[18] Univ Med Ctr Utrecht, Dept Med Genet, Utrecht, Netherlands

[19] Univ Med Ctr Utrecht, Rudolf Magnus Inst Neurosci, Utrecht, Netherlands

[20] Univ Calif Los Angeles, Semel Inst Neurosci & Human Behav, Ctr Neurobehav Genet, Los Angeles, CA USA

[21] Wellcome Trust Sanger Inst, Cambridge, England

[22] Harvard Univ, Broad Inst, Boston, MA 02115 USA

[23] MIT, Boston, MA USA

[24] Univ Bonn, Life & Brain Ctr, Dept Genom, D-53127 Bonn, Germany

[25] Univ Aberdeen, Inst Med Sci, Aberdeen, Scotland

[26] Kings Coll London, Inst Psychiat, Social Genet & Dev Psychol Ctr, London WC2R 2LS, England

来源：

BIOLOGICAL PSYCHIATRY | 2011年 / 70卷 / 01期

基金：

英国医学研究理事会;

关键词：

Diabetes type II; genetic risk variants; rs7903146; schizophrenia; TCF7L2; GENOME-WIDE ASSOCIATION; DRUG-NAIVE PATIENTS; GLUCOSE-TOLERANCE; DEMENTIA-PRAECOX; BLOOD-SUGAR; GENE; LOCI; MELLITUS; INSULIN; IMMUNOREACTIVITY;

D O I：

10.1016/j.biopsych.2011.01.031

中图分类号：

Q189 [神经科学];

学科分类号：

071006 ;

摘要：

Background: Schizophrenia is associated with increased risk of type II diabetes and metabolic disorders. However, it is unclear whether this comorbidity reflects shared genetic risk factors, at-risk lifestyle, or side effects of antipsychotic medication. Methods: Eleven known risk variants of type II diabetes were genotyped in patients with schizophrenia in a sample of 410 Danish patients, each matched with two healthy control subjects on sex, birth year, and month. Replication was carried out in a large multinational European sample of 4089 patients with schizophrenia and 17,597 controls (SGENE+) using Mantel-Haenszel test. Results: One type II diabetes at-risk allele located in TCF7L2, rs7903146 [T], was associated with schizophrenia in the discovery sample (p = .0052) and in the replication with an odds ratio of 1.07 (95% confidence interval 1.01-1.14, p = .033). Conclusion: The association reported here with a well-known diabetes variant suggests that the observed comorbidity is partially caused by genetic risk variants. This study also demonstrates how genetic studies can successfully examine an epidemiologically derived hypothesis of comorbidity.

引用

页码：59 / 63

页数：5

共 50 条

[21] Type 2 Diabetes Significantly Modulates the Impact of TCF7L2 rs7903146 Variant on the Risk of Coronary Atherosclerosis
Muendlein, Axel
Saely, Christoph H.
Geller-Rhomberg, Simone
Sonderegger, Gudrun
Rein, Philipp
Winder, Thomas
Beer, Stefan
Breuss, Johannes F.
Vonbank, Alexander
Drexel, Heinz
DIABETES, 2009, 58 : A199 - A199
[22] TYPE 2 DIABETES SIGNIFICANTLY MODULATES THE IMPACT OF TCF7L2 RS7903146 VARIANT ON THE RISK OF CORONARY ATHEROSCLEROSIS
Muendlein, A.
Saely, C.
Rhomberg, S.
Sonderegger, G.
Rein, P.
Winder, T.
Beer, S.
Breuss, J.
Vonbank, A.
ATHEROSCLEROSIS SUPPLEMENTS, 2009, 10 (02)
[23] IMPACTS OF A DIABETES POLYGENIC RISK SCORE AND VARIANT AT TCF7L2 ON GLUCOSE HOMEOSTASIS IN CYSTIC FIBROSIS
Porter, M.
Moran, A.
Lewis, C.
Blackman, S. M.
PEDIATRIC PULMONOLOGY, 2020, 55 : S80 - S81
[24] Impact of the TCF7L2 rs7903146 type 2 diabetes risk variant on clinical presentation in recently diagnosed patients with type 2 diabetes
Hansen, A. L.
Engelhard, L. M.
Brons, C.
Jessen, N.
Nielsen, J. S.
Vestergaard, P.
Hojlund, K.
Andersen, M. K.
Hansen, T.
Olsen, M. H.
Thomsen, R. W.
Sorensen, H. T.
Vaag, A.
DIABETOLOGIA, 2023, 66 (SUPPL 1) : S128 - S128
[25] TCF7L2, a risk gene for type 2 diabetes, is associated with cystic fibrosis-related diabetes
Blackman, S. M.
Hsu, S.
Ritter, S. E.
Naughton, K. M.
Bowers, A.
Cutting, G. R.
PEDIATRIC PULMONOLOGY, 2007, : 265 - 265
[26] TCF7L2 gene polymorphism as a risk for type 2 diabetes mellitus and diabetic microvascular complications
Aboelkhair, Noran Talaat
Kasem, Heba Elsayed
Abdelmoaty, Amera Anwar
El-Edel, Rawhia Hassan
MOLECULAR BIOLOGY REPORTS, 2021, 48 (06) : 5283 - 5290
[27] TCF7L2 gene polymorphism as a risk for type 2 diabetes mellitus and diabetic microvascular complications
Noran Talaat Aboelkhair
Heba Elsayed Kasem
Amera Anwar Abdelmoaty
Rawhia Hassan El-Edel
Molecular Biology Reports, 2021, 48 : 5283 - 5290
[28] Mechanisms by which common variants in the TCF7L2 gene increase risk of type 2 diabetes
Lyssenko, Valeriya
Lupi, Roberto
Marchetti, Piero
Del Guerra, Silvia
Orho-Melander, Marju
Almgren, Peter
Sjogren, Marketa
Ling, Charlotte
Eriksson, Karl-Fredrik
Lethagen, Asa-Linda
Mancarella, Rita
Berglund, Goran
Tuomi, Tiinamaija
Nilsson, Peter
Del Prato, Stefano
Groop, Leif
JOURNAL OF CLINICAL INVESTIGATION, 2007, 117 (08): : 2155 - 2163
[29] The TCF7L2 locus and type I diabetes
Qu, Hui-Qi
Polychronakos, Constantin
BMC MEDICAL GENETICS, 2007, 8
[30] Common variant at TCF7L2 gene is associated with increased risk of retinopathy in type 2 diabetic patients
Naghshpour, P.
Keshavarz, P.
Abbasour, S.
EUROPEAN JOURNAL OF HUMAN GENETICS, 2018, 26 : 1017 - 1017

← 1 2 3 4 5 →